1. Field of the Invention
The various embodiments of the present invention relate to the use of non-toxic soluble calcium compositions prior to administration of any fluoride-containing composition to enhance the anticaries effect of the fluoride compositions. More particularly, calcium compositions in any suitable form including mouth rinse, dentifrice, lozenge, confection, chewing gum and the like are administered prior to use of a fluoride-containing composition to enhance the formation of calcium-bound fluoride in plaque, on teeth and in oral tissue. The fluoride-containing compositions may be any conventional fluoride-containing products such as a fluoride rinse or a dentifrice.
2. Summary of the Related Art
Fluoride is believed to be beneficial in reducing the prevalence of dental caries. It has been demonstrated that even a small increase in the fluid concentration of fluoride in the oral cavity may have a significant effect on these processes (Featherstone, 2000, J Am. Dent. Assoc. 131:887-99). Studies have assessed whether the formation of bioavailable fluoride reservoirs may maintain the concentration of fluoride in plaque fluid and saliva after application of a conventional fluoride-containing rinse or dentifrice (White et al., 1994, Adv. Dent. Res. 8:166-74; Vogel et al., 1992, J Dent. Res. 71:448-52; Margolis and Moreno, 1990, J Dent. Res. 69 (Spec. Issue):606-13; ten Cate and Duijsters, 1983, Caries Res. 17:193-99).
Among the most important “labile” oral fluoride reservoirs is calcium fluoride, CaF2, or phosphate contaminated “calcium fluoride-like” deposits. Recent studies by Rose et al. (1996, Caries Res. 30-458-64) have suggested that much of the “labile” fluoride in plaque is bound to bacteria via calcium bridges. Regardless of the particular form, calcium appears to have a significant role in the formation of calcium-fluoride (“Ca—F”) deposits. Unfortunately, Ca—F deposition in the mouth is limited by the low concentration of unbound, or bioavailable, oral calcium. Furthermore, if a high level of calcium is administered simultaneously with fluoride, very rapid CaF2 formation occurs in the mouth with limited penetration into oral tissue.
Several approaches have been proposed to overcome these problems. One approach has been a two-part fluoride-releasing system in which fluoride first is released by the controlled hydrolysis of sodium hexafluorosilicate and subsequently reacts with calcium to induce a controlled “in depth” deposition of calcium-bound fluoride. Although studies have shown an increase in oral fluoride in saliva and plaque (Vogel et al., 1992, J Dent. Res. 71:448-52) and a reduction in the in vivo growth of caries lesions (Chow et al., 2000, J Dent. Res. 79:991-95), this approach has a number of limitations. First, this approach requires the formulation of commercially acceptable dentifrices and rinses compatible with a particular and unique chemistry. Second, this approach uses a fluoride source (Na2SiF6) that has not yet been approved by the Food and Drug Administration.
Other approaches to increasing fluoride deposition utilize two components: either (1) a dual compartment delivery device in which both components are simultaneously delivered (Kaufman et al., 1999, J Clin. Dent. 10:50-54; U.S. Pat. No. 6,387,352 to Johansen; U.S. Pat. Nos. 6,159,448 and 6,159,449 to Winston; U.S. Pat. Nos. 5,427,768 and 5,437,857 to Tung; U.S. Pat. Nos. 5,145,668 and 5,476,647 to Chow) or (2) procedures in which the two components are sequentially applied (Borovkii and Agafonov, 1994, Stomatologiia 1-5; U.S. Pat. No. 4,397,837 to Raaf; U.S. Pat. No. 4,083,955 to Grabenstetter). In one example of the sequential procedure, phosphate and fluoride are used as one component and calcium is used as the other component in order to increase the formation of caries-resistant fluoridated tooth mineral (Ca10(PO4)6F2). Use of phosphate, however, leads to an undesirable formation of insoluble fluorapatite in plaque and in soft tissue, rather than the desirable formation of bioavailable Ca—F deposits in these substrates.
Prior attempts to administer calcium before a fluoride product that did not include phosphate have shown little or no beneficial effects on the efficacy of the fluoride product. Blake-Haskins et al., (J Dent. Res. 1992; 71:1482-1486). Found that by simulating a 4.5 mMol/L calcium pre-rinse with a fluoride dentifrice in an in vitro experimental caries model, a lesion was reduced in size only 14% as compared to the use of a fluoride dentifrice alone. Similarly, Whitford et al. 2005 (Caries Res. 39: in press) found that a 20 mmol/L CaCl2 pre-rinse used immediately before brushing with a F dentifrice had no effect on human whole plaque F concentrations when samples were collected 1 h and 12 h after brushing).
In contrast to studies using low concentrations of calcium, U.S. Pat. No. 4,606,912 to Rudy and U.S. Pat. Nos. 5,476,647 and 5,891,448 to Chow and Takagi disclose administration of relatively high levels of calcium in a phosphate-free system. These patents disclose a calcium complexing agent that is used to control Ca—F formation. These systems, however, require mixing of the calcium and fluoride components before use.
U.S. Pat. No. 6,159,449 to Winston and Usen discloses another system for increasing salivary fluoride concentration. In this system, calcium and fluoride solids are dispersed in a non-aqueous, water-miscible vehicle. Calcium and fluoride ions are simultaneously released when the product contacts saliva or other aqueous solution.